Fig. 5: Bach1 deficiency in the hypernecrotic B6.Sst1^S murine model of Mtb infection enhances host antioxidant and reduces lung pro-inflammatory responses.

a–c, B6.Sst1^S and B6.Sst1^SBach1^−/− mice were infected at low dose with Mtb. Mice were euthanized at 17 dpi and single-cell suspensions from lungs were isolated from Mtb-infected and uninfected animals for RNA-seq analysis (n = 3–4 per group, samples obtained from 1 experiment). a, Volcano plots from DEGs identified. The comparison betweengroups is indicated. Differentially expressed genes are represented in red, genes with log₂FC > 1.4 and <- 1.4 are in green, genes with FDR < 0.05 are in blue and genes that are not significant are in grey. b, Enrichment analysis plots displaying the augmented pathways from the identified DEGs in the comparisons as indicated. Dot sizes represent the gene ratio in the pathway, fill colours are the FDR values. c, Heat map of FRG DEGs associated with induction (top) and suppression (bottom) of ferroptosis identified in the Mtb-infected and uninfected B6.Sst1^S and B6.Sst1^SBach1^−/− mice. Coloured row at the top of each panel corresponds to groups of mice analysed. d, Total antioxidant status (B6.Sst1^S n = 14 vs B6.Sst1^SBach1^−/− n = 17; two-tailed Mann–Whitney U-test), e, GSH (B6.Sst1^S n = 15 vs B6.Sst1^SBach1^−/− n = 16; two-tailed Mann–Whitney U-test) and f, MDA levels (B6.Sst1^S n = 13 vs B6.Sst1^SBach1^−/− n = 16; two-tailed Mann–Whitney U-test) measured in lung homogenates from Mtb-infected mice at 35 dpi. Pooled data from 3 independent experiments are shown and each dot denotes an individual animal. g, Heat map visualization of 10 cytokines/chemokines measured in lung homogenates from Mtb-infected B6.Sst1^S (n = 15) and B6.Sst1^SBach1^−/− (n = 17) mice (pooled from 3 independent experiments). Data shown in d–f are presented as mean ± s.e.m. Statistical significance was assessed using the Mann–Whitney test for the indicated experimental conditions.

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